Molecular biomedicine最新文献

{"title":"Glioblastoma: epidemiology, molecular pathogenesis, diagnosis, management, and therapeutic resistance.","authors":"Ji-Yong Sung, Kihwan Hwang","doi":"10.1186/s43556-026-00467-8","DOIUrl":"https://doi.org/10.1186/s43556-026-00467-8","url":null,"abstract":"<p><p>Glioblastoma (GBM) remains the most common and lethal primary malignant brain tumor in adults, with a median survival of approximately 15 months despite maximal multimodal therapy. The 2021 WHO classification has improved diagnostic precision by incorporating key molecular features, including EGFR amplification, TERT promoter mutation, PTEN loss, and MGMT promoter methylation. However, current standard of care treatments such as surgical resection, radiotherapy, temozolomide, and tumor treating fields have reached a therapeutic plateau, highlighting the urgent need for new therapeutic strategies. Although immunotherapy has transformed the treatment of several solid tumors, its clinical benefit in GBM remains limited. This limitation reflects not only low tumor mutational burden or blood brain barrier constraints, but also the profound spatial and temporal heterogeneity of the tumor. Distinct tumor regions exhibit diverse immune states, while ongoing clonal evolution dynamically reshapes antigenicity, immune recognition, and therapeutic response. In this review, we provide a comprehensive overview of glioblastoma, including epidemiology, molecular pathogenesis, diagnostic approaches, tumor microenvironment, intratumoral heterogeneity, and current therapeutic strategies. We further synthesize recent advances in spatial and longitudinal profiling technologies to describe the dynamic tumor immune ecosystem. We discuss how spatial compartmentalization and evolutionary processes collectively drive immune escape and therapeutic resistance, and highlight emerging strategies including adaptive immunotherapy, precision targeted delivery, and multimodal monitoring to overcome these challenges.</p>","PeriodicalId":74218,"journal":{"name":"Molecular biomedicine","volume":"7 1","pages":""},"PeriodicalIF":10.1,"publicationDate":"2026-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147847217","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The m⁶A reader IGF2BP2 promotes hepatocellular carcinoma progression via enhancing RELB stability.","authors":"Hehua Ma, Yuxin Hong, Zhi Xu, Zuyi Weng, Yuanxun Yang, Wei Song, Juan Li","doi":"10.1186/s43556-026-00465-w","DOIUrl":"https://doi.org/10.1186/s43556-026-00465-w","url":null,"abstract":"<p><p>N⁶-methyladenosine (m⁶A) modifications play a vital role in hepatocellular carcinoma (HCC) progression. However, the function of m⁶A reader proteins in HCC remains poorly understood. Here, we elucidate the role and mechanism of insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) in HCC. In here, we analyzed IGF2BP2 expression in HCC using bioinformatics and clinical samples. The functional role of the IGF2BP2-RELB regulatory axis in HCC progression was assessed through cytological assays and a xenograft HCC mouse model. RNA sequencing, Western blotting, Actinomycin-D assays, and RNA immunoprecipitation (RIP) and methylated RNA immunoprecipitation (MeRIP) assays were performed to investigate the regulatory mechanisms of IGF2BP2 on RELB expression. We found high expression of IGF2BP2 in HCC was positively correlated with poor prognosis. Gain- and loss-of-function assays demonstrated that IGF2BP2 was essential for HCC cell proliferation and migration. IGF2BP2 directly bound to RELB mRNA and enhanced its stability via the KH3/4 domain. Upregulated RELB promoted nuclear translocation of the RELB:p52 dimer, leading to activation of the NF-κB signaling pathway. Furthermore, inhibition of IGF2BP2 and RELB suppressed HCC tumor progression both in vitro and in vivo. Our study demonstrates that IGF2BP2 plays a critical role in HCC progression by stabilizing RELB mRNA and activating the NF-κB signaling pathway. The results suggest that IGF2BP2 may be a potential therapeutic strategy for HCC.</p>","PeriodicalId":74218,"journal":{"name":"Molecular biomedicine","volume":"7 1","pages":""},"PeriodicalIF":10.1,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147847224","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Complement factor H supplementation rather than complete C3 knockout provides therapeutic benefits in IgA nephropathy.","authors":"Xianzhi Li, Xinran Ni, Xiaohan Yuan, Huan Wu, Sufang Shi, Lijun Liu, Jicheng Lv, Hong Zhang, Li Zhu","doi":"10.1186/s43556-026-00463-y","DOIUrl":"10.1186/s43556-026-00463-y","url":null,"abstract":"<p><p>IgA nephropathy (IgAN), the most common primary glomerulonephritis worldwide, is characterized by mesangial IgA deposition, which triggers complement activation, primarily through the alternative pathway. While complement dysregulation contributes to kidney injury and adverse outcomes, complement may also facilitate clearance of pathogenic immune complexes. Here, we compared complete complement component 3 (C3) deficiency with supplementation of complement factor H (Cfh), the principal regulator of alternative pathway, in murine IgAN models. C3 deficiency prevented complement activation but paradoxically increased glomerular IgA deposition and macrophage infiltration, resulting in complicated inflammatory response. In contrast, Cfh supplementation reduced glomerular IgA and C3 deposition, decreased inflammatory cytokine expression, attenuated macrophage infiltration, lessened glomerular area and ameliorated proteinuria while enhancing macrophage-mediated phagocytosis of circulating IgA immune complexes. Accordingly, IgAN patients with higher plasma CFH levels exhibited reduced mesangial IgA and C3 deposition alongside elevated circulating C3 levels, supporting CFH's protective role in regulating complement activation and promoting immune complex clearance. Our results reveal complement's dual role in IgAN: promoting inflammatory kidney injury while facilitating clearance of pathogenic IgA deposits. Targeted complement regulation via complement factor H supplementation, rather than complete complement inhibition via global complement component 3 knockout, achieves superior therapeutic effects by simultaneously controlling complement activation, enhancing immune complex clearance, suppressing inflammation, and reducing proteinuria. These findings identify complement factor H as a novel and promising therapeutic strategy for IgA nephropathy through targeted complement regulation.</p>","PeriodicalId":74218,"journal":{"name":"Molecular biomedicine","volume":"7 1","pages":""},"PeriodicalIF":10.1,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13133335/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147791388","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epigenetic modifications in cancer drug resistance: molecular mechanisms and therapeutic interventions.","authors":"Jingyi Yang, Minpu Zhang, Yuting Zhong, Changgang Sun, Jing Zhuang","doi":"10.1186/s43556-026-00458-9","DOIUrl":"10.1186/s43556-026-00458-9","url":null,"abstract":"<p><p>Therapeutic resistance remains a major cause of treatment failure and disease recurrence across cancer types, considerably limiting the long-term efficacy of chemotherapies, targeted therapies, and immunotherapies. Growing evidence indicates that resistance cannot be fully explained by static genetic alterations but rather arises from dynamic and reversible adaptive processes. Epigenetic regulation governs transcriptional plasticity, cellular state transitions, and tumor heterogeneity under therapeutic stress. Alterations in DNA methylation, histone modifications, chromatin accessibility, and non-coding RNA networks enable cancer cells to silence tumor suppressor programs, activate compensatory survival pathways, acquire stem cell-like drug-tolerant persister states, and remodel the tumor immune microenvironment. These mechanisms often act in a coordinated manner to form a dynamic regulatory system that supports adaptive resistance. However, current studies have frequently focused on individual epigenetic regulators and have lacked an integrated framework to explain how epigenetic plasticity collectively drives therapeutic resistance. In this review, we deconstruct cancer therapy resistance using the conceptual framework of the \"epigenetic landscape.\" We summarize the molecular functions and crosstalk among the major epigenetic layers and describe how this integrated network sustains key resistance-associated phenotypes. We also discuss emerging therapeutic strategies that target epigenetic plasticity, including epigenetic drugs, targeted protein degradation, epigenetic editing, and rational combination therapies. Overall, this review provides a systematic framework for understanding epigenetically mediated therapy resistance and highlights epigenetic plasticity as a therapeutic vulnerability for developing durable cancer treatments.</p>","PeriodicalId":74218,"journal":{"name":"Molecular biomedicine","volume":"7 1","pages":""},"PeriodicalIF":10.1,"publicationDate":"2026-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13129053/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147791413","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Subarachnoid hemorrhage: epidemiology, risk factors, pathogenesis, and clinical therapies.","authors":"Hangyu Shen, Xu Yan, Mingyue Zhao, Jie Sun, Yi Huang","doi":"10.1186/s43556-026-00455-y","DOIUrl":"https://doi.org/10.1186/s43556-026-00455-y","url":null,"abstract":"<p><p>Subarachnoid hemorrhage (SAH) is an extremely lethal cerebrovascular emergency that can lead to severe long term neurological deficits. Modern research evidence indicates that the incidence of SAH varies significantly across different regions and populations, and this variation is determined by the interaction between non-modifiable factors (such as age, gender, family history, and genetic susceptibility) and modifiable factors (such as hypertension, smoking, drug use, and metabolic disorders). Advancements in vascular biology and genomics further suggest that extracellular matrix instability, endothelial dysfunction, chronic inflammation, and population-specific genetic variations play crucial roles in aneurysm formation and rupture. After aneurysm rupture, SAH triggers a biphasic injury cascade. Early brain injury (EBI) occurs within minutes to hours, manifesting as a sudden increase in intracranial pressure, systemic hypoperfusion, blood brain barrier disruption, neuroinflammation, cerebral edema, and metabolic failure. These early disturbances create favorable conditions for delayed cerebral ischemia (DCI), which occurs several days later due to microvascular dysfunction, impaired neurovascular coupling, cortical spreading depolarization, and progressive immunometabolic changes. Understanding this mechanistic continuum is of great significance for early detection and selection of treatment targets. Recent advancements in neuroimaging, biomarker development, and multimodal monitoring have improved diagnostic accuracy, while current management measures include rapid aneurysm fixation, optimized intensive care, and emerging neuroprotective strategies. Despite these advancements, treatment outcomes remain suboptimal, highlighting the need for further improvements in risk stratification, mechanism-based interventions, and population specific preventive measures. This review synthesizes the latest knowledge on the epidemiology, risk factors, pathogenesis, and clinical management of SAH to support a more comprehensive research and care framework.</p>","PeriodicalId":74218,"journal":{"name":"Molecular biomedicine","volume":"7 1","pages":""},"PeriodicalIF":10.1,"publicationDate":"2026-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13121685/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147791406","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: UCHL5 is a putative prognostic marker in renal cell carcinoma: a study of UCHL family.","authors":"Mengdi Zhang, Jingxian Li, Sijia Liu, Fangfang Zhou, Long Zhang","doi":"10.1186/s43556-026-00449-w","DOIUrl":"https://doi.org/10.1186/s43556-026-00449-w","url":null,"abstract":"","PeriodicalId":74218,"journal":{"name":"Molecular biomedicine","volume":"7 1","pages":""},"PeriodicalIF":10.1,"publicationDate":"2026-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13121667/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147791403","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development and characterization of 3D spinal cord organoids to advance the study of amyotrophic lateral sclerosis.","authors":"Matteo Bordoni, Eveljn Scarian, Letizia Messa, Maria Garofalo, Emanuela Jacchetti, Manuela Teresa Raimondi, Luca Diamanti, Stella Gagliardi, Stephana Carelli, Cristina Cereda, Orietta Pansarasa","doi":"10.1186/s43556-026-00453-0","DOIUrl":"https://doi.org/10.1186/s43556-026-00453-0","url":null,"abstract":"","PeriodicalId":74218,"journal":{"name":"Molecular biomedicine","volume":"7 1","pages":""},"PeriodicalIF":10.1,"publicationDate":"2026-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13109475/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147791434","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PFKP is required for chemoresistant phenotype of breast cancer through modulating the formation of CD133⁺ cancer stem like cells.","authors":"Kai Fang, Yue Ma, Lihua Li, Yan Yue, Hang Ruan, Sidong Xiong","doi":"10.1186/s43556-026-00454-z","DOIUrl":"https://doi.org/10.1186/s43556-026-00454-z","url":null,"abstract":"<p><p>Breast cancer is the foremost cause of cancer-related death in women globally, and taxane-anthracycline (TA) combination regimens represent standard frontline chemotherapy. Although widely administered, the pathological complete response rate to TA therapy is less than 30%, and chemoresistance remains a major barrier to effective disease control, frequently leading to relapse and poor survival. Both metabolic reprogramming and tumor microenvironmental remodeling are closely associated with treatment failure, yet how they interact to drive TA resistance remains largely unclear. Here we show that phosphofructokinase platelet (PFKP), a key glycolytic enzyme, is highly expressed in breast cancer. PFKP drives glycolysis and promotes CD133⁺ cancer stem-like cells (CSLCs) that are inherently TA-resistant. Moreover, PFKP-overexpressing cancer cells stimulate cancer-associated fibroblasts (CAFs), which in turn augment CD133⁺ CSLC formation via the CXCL16/CXCR6 axis, establishing a feedforward loop that reinforces chemoresistance. These results reveal a previously unappreciated mechanism by which a glycolytic enzyme in cancer cells orchestrates stromal crosstalk to sustain a chemotherapy-refractory niche. By identifying PFKP as a key driver and the PFKP-CSLC-CAF axis as an actionable target, our work moves the field beyond the traditional view of metabolic reprogramming as a cell-autonomous event. Disrupting this axis-for instance, by PFKP inhibition or CXCL16/CXCR6 blockade-may restore TA sensitivity in aggressive basal-type breast cancer, offering a promising strategy to improve long-term outcomes for hard-to-treat patients.</p>","PeriodicalId":74218,"journal":{"name":"Molecular biomedicine","volume":"7 1","pages":""},"PeriodicalIF":10.1,"publicationDate":"2026-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13106758/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147791439","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"DNA and RNA editing for the therapy of human diseases: current status, challenges, and future prospects.","authors":"Rui Zhao, Changli Wang, Jiamei Li, Yan Liao, Chenwei Huang, Ting Hu, Haoling Zhang, Wangzheqi Zhang","doi":"10.1186/s43556-026-00456-x","DOIUrl":"https://doi.org/10.1186/s43556-026-00456-x","url":null,"abstract":"<p><p>The rapid development of DNA- and RNA-editing tools (collectively referred to as gene editing technologies) has caused a paradigm shift in the treatment of human diseases from symptomatic treatment to precision-based medicine. Both DNA-based and RNA-based editing systems, including Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-derived technologies and newly developed RNA editing tools, have pushed technological frontiers in terms of editing precision, hierarchical control, and reversibility; they have accumulated a growing body of preclinical and clinical evidence across diverse diseases ranging from inherited disorders to cancer, infectious diseases, and neurodegenerative diseases (ND). This review systematically summarizes the core principles and representative advances of DNA-based genome editing and RNA-based transcriptome editing technologies, comprehensively compares the two categories of technical strategies in terms of therapeutic potential, durability of effects, and risk profiles, and further explores the key challenges for achieving long-term safe and efficient in vivo applications, covering core bottlenecks such as delivery efficiency, tissue specificity, genotoxicity, and immunogenicity. Safety assessment has broadened to include tracking genotoxicity and genomic structural variations, whereas delivery systems and tissue specificity are determinant factors for in vivo therapeutic applications. Through the employment of both permanent and reversible editing strategies with high cargo-writing capacity and low integration risk, combined with programmable delivery systems, the therapeutic potential of hard-to-transfect tissues and complex diseases is anticipated to be broadened, opening new paths for clinical translation.</p>","PeriodicalId":74218,"journal":{"name":"Molecular biomedicine","volume":"7 1","pages":""},"PeriodicalIF":10.1,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13103161/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147791361","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In vivo CAR-cell therapy: current challenges and emerging therapeutic advances.","authors":"Yi-Min Yang, Bo Bao, Yu-Hao Cao, Jin Yao, Yu-Fan Ding, Yi-Yang Hu, Fan Fan, Jun-Long Zhao","doi":"10.1186/s43556-026-00447-y","DOIUrl":"10.1186/s43556-026-00447-y","url":null,"abstract":"<p><p>In vivo chimeric antigen receptor (CAR) cell therapy is undergoing a transformative shift from conventional ex vivo manufacturing toward in situ cellular editing, aiming to generate functional CAR-engineered immune cells directly within patients through targeted vector delivery, thereby significantly enhancing therapeutic accessibility and applicability. While rapid advances have been made in both viral (lentiviral and adeno-associated viral vectors) and non-viral (lipid nanoparticle) delivery platforms, along with the expansion of effector cell lineages including CAR-T, CAR-NK, and CAR-M, critical translational bottlenecks remain. These include insufficient delivery precision, limited cellular persistence, immunosuppressive tumor microenvironment (TME) resistance, and challenges in safety controllability. This review systematically examines the working mechanisms and limitations of current delivery platforms for in vivo gene transfer. It provides a comprehensive comparison of how CAR-T, CAR-NK, and CAR-M platforms employ distinct yet complementary strategies to address tumor heterogeneity, solid tumor physical and immune barriers, and the specificity constraints of in situ editing. Furthermore, we highlight emerging frontiers such as artificial intelligence-guided personalized therapy design, smart delivery systems (logic-gated CARs, circular RNA vectors), and the development of multicellular synergistic \"synthetic immune systems.\" By integrating multidisciplinary perspectives, this review not only offers a comprehensive roadmap bridging fundamental mechanisms to clinical translation but also lays a theoretical and technical foundation for advancing the next generation of safe, precise, and efficacious in vivo CAR therapies.</p>","PeriodicalId":74218,"journal":{"name":"Molecular biomedicine","volume":"7 1","pages":""},"PeriodicalIF":10.1,"publicationDate":"2026-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13096480/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147730888","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}